This invention relates generally to a method for medical examination, in particular, radiographic imaging of organs using positron emitting radiopharmaceuticals.
The American Cancer Society estimates that in 2005 about 145,290 people will be diagnosed with colorectal cancer and that about 56,290 people will die of the disease in the United States. [American Cancer Society. Colorectal Cancer Facts & Figure, Special Edition 2005. Atlanta: American Cancer Society, 2005.] The great majority of these cancers and deaths could be prevented by wider use of established screening tests. Yet, cancers of the colon and rectum combined are the third most common type of cancer and the second most common cause of cancer death in the United States. Screening can prevent many cases of colorectal cancer because most colorectal cancers develop from adenomatous polyps. Polyps are non-cancerous growths in the colon and rectum. Detecting polyps through screening and removing them can actually prevent cancer from occurring.
Colonoscopy is the most effective method for screening colorectal cancer. In a screening colonoscopy procedure a physician visually examines the full length of colon for adenomatous polyps on the wall, which may be removed during the same procedure. Although colonoscopy is most sensitive among various screening methods for the detection of polyps and cancers, there is some probability that these abnormalities are missed especially when they are small or of shapes that are difficult to distinguish.
While colonoscopy screens colorectal cancer by seeking out morphological changes in the wall of colon, Positron Emission Tomography (PET) presents an opportunity to detect colorectal and other cancers based on their distinctive physiological signatures even at a stage of cancer development too early for morphological changes to be visually recognizable. PET is a radionuclide imaging method in which a positron emitting radiopharmaceutical such as [18F] fluoro-2-deoxy-D-glucose (FDG) is used to visualize metabolic processes in a patient. FDG is a radioactive analog of glucose, which is phosphorylated and trapped within cells. After a patient receives a dose of FDG he or she is examined with a scanner that is capable of detecting pairs of correlated gamma rays resulting from annihilations of positrons emitted from 18F nuclei. The coincident gamma rays travel along a line in opposite directions and are detected by a pair of opposing detectors in the PET scanner. The data collected from the scanner are used to reconstruct the distribution or three dimensional image of metabolic byproduct of FDG in a patient body. PET, using FDG (FDG-PET) as a tracer of tumor glucose metabolic activity, is an accurate non-invasive imaging technology which probes physiological functions of tissue and organ rather than their structures or morphologies. The increased rate of glycolysis in neoplastic or cancer cells, independent of the oxygen concentration present, has been previously reported. [O. Warburg, “On the origins of cancer cells,” Science, Vol. 123, 309-314 (1956)].
FDG-PET has been established as an effective tool for diagnosis of recurrent or metastatic colorectal cancer. The sensitivity (probability of correctly identifying a lesion) and specificity (probability of correctly identifying a non-lesion) of FDG-PET for the detection of recurrent disease have been reported as approximately 95% and 76%, respectively. [R. H. Huebner, K. C. Park, J. E. Shepherd, J. Schwimmer, J. Czernin, M. Phelps, S. Gambhir, “A meta-analysis of the literature for whole-body FDG PET detection of recurrent colorectal cancer,” Journal of Nuclear Medicine, Vol. 41, 1177-1189 (2000)] However, the sensitivity of PET for pre-malignant colon lesions and early stage colorectal cancer is very limited. This is especially true for flat, pre-malignant lesions, and protruded, pre-malignant lesions smaller than 3 cm and colon cancers smaller than 2 cm. [S. Friedland, R. Soetikno, M. Carlisle, A. Taur, T. Kaltenbach, G. Segall, “18-Fluorodeoxyglucose positron emission tomography has limited sensitivity for colonic adenoma and early stage colon cancer,” Gastrointestinal Endoscopy, Vol. 61(3), 395-400 (2005)]
This sensitivity limitation of PET is primarily attributable to poor spatial resolution of PET scanner and insufficient amount of positron annihilation data recorded in a typical imaging procedure for reconstructing a clinical image. A conventional PET typically yields reconstructed images with a spatial resolution of 8-15 mm, depending on the injected dose, imaging time, and intrinsic resolution of the scanner. Gamma ray pairs produced in positron annihilations in the field of view (FOV) must travel through intervening tissues to reach a pair of opposing detectors in a ring of detectors of PET scanner which is positioned outside and surrounding a patient or an imaging subject. A fairly large fraction of gamma rays is attenuated through absorption or scattered away from initial line of flight during the passage through intervening tissue. Among those gamma photons successfully leaving the patient body undisturbed only a small fraction falls within the limited geometric acceptance of PET scanner and is ultimately recorded. The loss of gamma rays through attenuation and scattering, and the limited geometric acceptance of PET scanner are two of the most significant factors limiting the amount of positron annihilation events recorded in a typical PET imaging procedure. Because of these inefficiencies inherent to a conventional PET a prolonged imaging time or a large dose of FDG is usually required to produce a clinical image of acceptable diagnostic quality.
A conventional PET also suffers from a large number of uncorrelated gamma rays (“singles”). The singles are recorded when one of gamma ray pairs emitted in positron annihilation events goes undetected by PET scanner for one reason or another, e.g., attenuation and scattering within tissues. A pair of singles can fake as a genuinely correlated pair of gamma rays (a random coincidence event) and enter the detection stream in spite of measures designed to discriminate against such occurrences. These random coincidence events incur a significant scanner dead time during which PET scanner remains ineffective and typically show up in the image as a burring background and reduce image contrast lowering diagnostic quality of the image. Similar, undesirable effects on the image result when one or both of correlated gamma rays from a positron annihilation event experiences a scatter in the patient body and deviates from its original line of flight before being detected and recorded as a genuine, prompt positron annihilation event (a scatter coincidence event).
A conventional PET is also one of the most expensive medical imaging modality due to the high price of a PET scanner, which is an important factor limiting wider spread use.
Uniqueness of colon anatomy presents an opportunity to implement the positron emission imaging in entirely different ways than a conventional PET. Colon is an elongate tubular organ with a thin, pliable wall, which can be regarded as a thin sheet of tissue rolled into a tube. The wall of entire length of colon is accessible from inside in minimally invasive manner through anus. This allows a pair of gamma detectors to be positioned with their radiation sensitive faces facing each other, and sandwiching and making contacts with a portion of folded colon wall of a small volume. The gamma detector pair is scanned over and across the colon wall area of interest during which the position of the gamma detector pair with respect to a fixed origin and coincidence gamma rays from positron annihilation events are recorded. The information thus obtained can be utilized to produce a planar image of the distribution of positron emitting radiopharmaceutical in the area of colon wall.
The proximity of the opposing pair of gamma detectors with an imaging subject provides many advantages. Because of the small volume covered by the FOV of the gamma detector pair the attenuation and scattering of gamma rays from positron annihilation events within the FOV are largely negligible. Because of the small size of gamma detectors, singles and random coincidence event rates contributed by tissues surrounding the gamma detector pair are very low and the detector dead time is negligible. The lack of attenuation and detector dead time of the present imaging method leads to a significant increase in the sensitivity for detecting true coincidence events resulting from positron annihilation events. Increase in sensitivity can be advantageously utilized to reduce imaging time and FDG dose, and to improve diagnostic quality of image. The proximity of gamma detectors with the imaging subject allows the spatial resolution of the imaging system to be primarily determined by the intrinsic resolution of the gamma detector pair, which in turn is highly dependent on the geometry of individual gamma detector and relative positional relationship of the gamma detector pair. In contrast the spatial resolution of PET is significantly influenced by factors other than the intrinsic resolution of the PET scanner, which is often difficult to control. Due to inherent simplicity the price of a new imaging system incorporating the present imaging method will be much lower than that of a conventional PET system.
In the past planar imaging methods utilizing positron emitting radiopharmaceuticals have been used to study the transport of radiopharmaceutical in a small imaging subject [S. Seigel, J. J. Vaquero, L. Aloj, J. Seidel, E. Jagoda, W. R. Gandler, W. C. Eckelman, M. V. Green, “Initial results from a PET/Planar small animal imaging system, ” IEEE Transactions on Nuclear Science, Vol. 46, No. 3, 571-575 (1999)] and to perform a dynamic study of radioactivity in arterial blood. [S. Shokouhi, S. Stoll, A Villanueva, P. Vaska, D. Schlyer, C. Woody, B. Yu, P. O'Connor, J. Pratte, V. Radeka, N. volkow, J. Fowler, “A non-invasive LSO-APD blood radioactivity monitor for PET imaging studies, ” IEEE Transactions on Nuclear Science, Vol. 50, 1447-1461 (2003); S. Rajeswaran, D. L. Bailey, S. P. Hume, D. W. Townsend, A. Geissbuhler, J. Young, T. Jones, , “2D and 3D imaging of small animals and the human radial artery with a high resolution detector for PET, ” IEEE Transactions on Nuclear Science, Vol. 11, No. 3, 386-391 (1992)] In these imaging methods the detectors are positioned outside a live imaging subject away from the main regions of interest and therefore there still exist some of drawbacks found in conventional PET.